Project Summary/Abstract New HIV infections among youth ages 13-24 comprise 22% of all new HIV infections in the US. More than 60,000 adolescents and young adults (AYA) are already living with HIV in the US, and new infections contribute substantially to HIV transmission. The HIV epidemic among US AYA demands new approaches to HIV diagnosis and prevention, with consideration of the challenges of health care delivery and research among AYA living with and at risk of acquiring HIV. Computer simulation health-policy models can add substantial value to clinical trials and observational studies by projecting outcomes beyond the time horizon of clinical studies. This is particularly important for AYA, in whom the effects of HIV infection and treatment may not manifest for many years. This mentored clinical scientist research career development award will allow the recipient, an infectious diseases physician at Massachusetts General Hospital, to develop a research career using modeling methods and cost-effectiveness analysis to evaluate current critical questions in HIV prevention and screening in US AYA. Reducing incident HIV infections, improving HIV screening, optimizing HIV pre-exposure prophylaxis services, and assessing HIV pre-exposure prophylaxis effectiveness are high- priority areas for the NIH Office of AIDS Research (2018 Goals) and NICHD (2017 New Research Priorities). Collaborating with national studies of AYA affected by HIV, this project will develop a new, comprehensive health policy model of HIV disease prevention, diagnosis and treatment in AYA. The model will reflect age- and developmentally-specific AYA patterns of care-seeking behaviors, including engagment in care and adherence to medications. The model will be used to evaluate the short- and long-term clinical outcomes and healthcare costs associated with the screening and prevention of HIV in US AYA, focusing on a key sub-population, young men who have sex with men.This work will build a foundation for future analyses of the delivery of HIV pre-exposure prophylaxis and other emerging screening, treatment and prevention modalities. This mentored research will be accompanied by relevant training in model development, derivation of trial-based model inputs, and performance of policy-relevant analyses. This research and career development training provide the recipient with a pathway to an independent career as a clinical investigator, focused on using modeling methodology to optimize care for adolescents and young adults affected by HIV.